Photodynamic Modulation of Type 1 Interferon Pathway on Melanoma Cells Promotes Dendritic Cell Activation

The immune response against cancer generated by type-I-interferons (IFN-1) has recently been described. Exogenous and endogenous IFN-α/β have an important role in immune surveillance and control of tumor development. In addition, IFN-1s have recently emerged as novel DAMPs for the consecutive events connecting innate and adaptive immunity, and they also have been postulated as an essential requirement for induction of immunogenic cell death (ICD). In this context, photodynamic therapy (PDT) has been previously linked to the ICD. PDT consists in the administration of a photosensitizer (PS) and its activation by irradiation of the affected area with visible light producing excitation of the PS. This leads to the local generation of harmful reactive oxygen species (ROS) with limited or no systemic defects. In the current work, Me-ALA inducing PpIX (endogenous PS) was administrated to B16-OVA melanoma cells. PpIX preferentially localized in the endoplasmic reticulum (ER). Subsequent PpIX activation with visible light significantly induced oxidative ER-stress mediated-apoptotic cell death. Under these conditions, the present study was the first to report the in vitro upregulation of IFN-1 expression in response to photodynamic treatment in melanoma. This IFN-α/β transcripts upregulation was concurrent with IRF-3 phosphorylation at levels that efficiently activated STAT1 and increased ligand receptor (cGAS) and ISG (CXCL10, MX1, ISG15) expression. The IFN-1 pa...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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Publication date: Available online 11 December 2019Source: Best Practice &Research Clinical Endocrinology &MetabolismAuthor(s): Giusy Elia, Silvia Martina Ferrari, Maria Rosaria Galdiero, Francesca Ragusa, Sabrina Rosaria Paparo, Ilaria Ruffilli, Gilda Varricchi, Poupak Fallahi, Alessandro AntonelliAbstractAnticancer immunotherapy, in the form of immune checkpoint inhibition (ICI), is a paradigm shift that has transformed the care of patients with different types of solid and hematologic cancers. The most notable improvements have been seen in patients with melanoma, non-small-cell lung, bladder, renal, cervical, u...
Source: Best Practice and Research Clinical Endocrinology and Metabolism - Category: Endocrinology Source Type: research
Tumor-infiltrating lymphocytes (TIL) are considered enriched for T cells recognizing shared tumor antigens or mutation-derived neoepitopes. We performed exome sequencing and HLA-A*02:01 epitope prediction from tumor cell lines from two HLA-A2-positive melanoma patients whose TIL displayed strong tumor reactivity. The potential neoepitopes were screened for recognition using autologous TIL by immunological assays and presentation on tumor major histocompatibility complex class I (MHC-I) molecules by Poisson detection mass spectrometry (MS). TIL from the patients recognized 5/181 and 3/49 of the predicted neoepitopes, respec...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
This report describes a 21‐year‐old man who was refractory to chemotherapy and immunotherapy. Whole exome sequencing and low‐depth whole genome sequencing confirmed the KRAS gene amplification, which may lead to the tumor cells’ progression and proliferation. After discussion at the molecular tumor board, the patient was offered paclitaxel, carboplatin, and sorafenib (CPS) based on a phase III clinical trial of melanoma with KRAS gene copy gains. After treatment with CPS, the patient achieved excellent curative effects. Because of a nearly 50% frequency of KRAS amplification in chemotherapy‐refractory testicu...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Precision Medicine Clinic: Molecular Tumor Board Source Type: research
Cancer immunology drugs, which harness the body ’s immune system to better attack cancer cells, have significantly changed the face of cancer treatment. People with aggressive cancers are now living longer, healthier lives. Unfortunately, cancer immunology therapy only works in a subset of patients.Now, a new study from scientists at the UCLA Jonsson Comprehensive Cancer Center helps explain why some people with advanced cancer may not respond to one of the leading immunotherapies, PD-1 blockade, and how a new combination approach may help overcome resistance to the immunotherapy drug.TheUCLA study, published today i...
Source: UCLA Newsroom: Health Sciences - Category: Universities & Medical Training Source Type: news
The effect of health insurance on management and outcomes in melanoma is unclear. Using the National Cancer Database (NCDB), we evaluated the effect of insurance on (1) stage at diagnosis, (2) receipt of immunotherapy, and (3) overall survival (OS) among patients with melanoma. We included patients with stage I–IV melanoma diagnosed from 2011 to 2015. Patients were stratified by age (below 65 vs. 65 y or above) and insurance (commercial, Medicare, Medicaid and uninsured). We evaluated the association between insurance and (1) stage at diagnosis (stage I–III vs. IV) and (2) receipt of immunotherapy (stage...
Source: Journal of Immunotherapy - Category: Allergy & Immunology Tags: Review Articles Source Type: research
Immune-checkpoint inhibitors have revolutionized the treatment of cancers in recent years. Four drugs have obtained FDA approval in a variety of cancer types. Immune-related adverse events are common and occur in up to 60% of treated patients. Common manifestations of immune-related adverse events include rash, colitis, hepatitis, and hypophysitis. Most cases are mild to moderate in grade; however, severe manifestations with lethal outcomes have been described. Acute kidney injury is reported as a rare complication. In this case report, we present a patient with metastatic melanoma undergoing combined immune-checkpoint inh...
Source: Journal of Immunotherapy - Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Conclusions: These studies suggest that in addition to its role as a palliative therapeutic modality, RFA may have clinical potential as an immune-adjuvant therapy by augmenting the efficacy of adoptive T cell therapy. PMID: 31795828 [PubMed - in process]
Source: International Journal of Hyperthermia - Category: Internal Medicine Tags: Int J Hyperthermia Source Type: research
Authors: Hurwitz MD Abstract Hyperthermia holds great promise to advance immunotherapy in the treatment of cancer. Multiple trials have demonstrated benefit with the addition of hyperthermia to radiation or chemotherapy in the treatment of wide-ranging malignancies. Similarly, pre-clinical studies have demonstrated the ability of hyperthermia to enhance each of the 8 steps in the cancer-immunotherapy cycle including stimulation of tumor-specific immunity. While there has been an extensive recent focus on augmenting immunotherapy with radiation, surprisingly to date, there have been no clinical trials assessing the ...
Source: International Journal of Hyperthermia - Category: Internal Medicine Tags: Int J Hyperthermia Source Type: research
Authors: Han RH, Dunn GP, Chheda MG, Kim AH Abstract Metastases from melanoma, lung and breast cancer are among the most common causes of intracranial malignancy. Standard of care for brain metastases include a combination of surgical resection, stereotactic radiosurgery, and whole-brain radiation. However, evidence continues to accumulate regarding the efficacy of molecularly-targeted systemic treatments and immunotherapy. For non-small cell lung cancer (NSCLC), numerous clinical trials have demonstrated intracranial activity for inhibitors of EGFR and ALK. Patients with melanoma brain metastases may benefit from ...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Although mesothelioma is the consequence of a protracted immune response to asbestos fibers and characterized by a clear immune infiltrate, novel immunotherapy approaches show less convincing results as compared to those seen in melanoma and non-small cell lung cancer. The immune suppressive microenvironment in mesothelioma is likely contributing to this therapy resistance. Therefore, it is important to explore the characteristics of the tumor microenvironment for explanations for this recalcitrant behavior. This review describes the stromal, cytokine, metabolic, and cellular milieu of mesothelioma, and attempts to make co...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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